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9 January 2023The Molecular Oncology group has determined that ABCC3 correlates with worse survival, a poor response to treatments and could favor the reappearance of the disease
The discovery, obtained in collaboration with Spanish, Belgian and Slovenian researchers, has been published in the prestigious magazine 'Scientific Reports'
The Molecular Oncology group of the Aragón Health Research Institute (IIS Aragón) has studied glioblastoma, the brain tumor with the worst prognosis in adults, and has identified ABCC3 as a possible biomarker for this tumor, since it correlates with worse survival, poor response to treatments and could favor the appearance of recurrences. The work, whose results have been published in the prestigious magazine Scientific Reports, has been carried out in collaboration with researchers from the National Cancer Research Center, the Vrije Universiteit Brussel (Belgium) and the University of Ljubljana (Slovenia).
El Molecular Oncology group, led by the researcher ARAID Alberto Jiménez Schuhmacher has developed nanoantibodies against specific regions of ABCC3 that have been validated in different in vivo experimental models and that could be used to develop various biomedical applications.
“Big data is revolutionizing cancer research, since being able to have massive data from samples of cancer patients makes it possible to identify many alterations that could have medical utility. However, despite the fact that brain tumors are transforming their molecular characterization, many of these findings do not translate into advances in clinical practice. This is due, in part, to the lack of non-invasive biomarkers and the limitations imposed by the blood-brain barrier, a membrane that acts as a highly selective filter in the brain”, explains Schuhmacher, ARAID researcher at IIS Aragón.
Thus, hundreds of samples from patients with glioblastoma have been analyzed to look for the genes that are "more expressed, more turned on." “These genes were not expressed, they were turned off in healthy brains”, explains Schuhmacher. “We studied whether they correlated with survival, response to treatment, and the ability to form recurrences, and we selected ABCC3 as a target against which to develop biotechnological tools for the diagnosis of these tumors,” she points out.
Once the biomarker was identified, the IIS Aragón researchers studied the most important regions of the ABCC3 protein against which they could develop nanoantibodies, special proteins that stick very specifically to the target against which they are designed. "We selected three regions and isolated nanobodies against them using a collection that contains one hundred million of them," says Eduardo Ruiz López, first author of the work and who has carried out this research thanks to a pre-doctoral grant from the Spanish Association Against Cancer. (AECC). “We characterized and validated various nanoantibodies against ABCC3, first in cell models and then in different experimental models”, he adds.
The next challenge consisted in analyzing whether these nanobodies could detect brain tumors in mouse models, since they had to cross the blood-brain barrier. These are membranes that act as a selective filter in the brain and protect from many damages and toxic agents, but in return they prevent many molecules from reaching the brain. “We have seen that these nanobodies detect glioblastoma equally in models that present different degrees of rupture of the blood-brain barrier, which suggests that they could cross it”, points out Ruiz López.
Once validated in in vivo experimental models, these nanobodies could be used for the development of various biomedical applications ranging from diagnostic imaging to the development of support tools in surgery or the design of new treatments. "But there is still a long way to go, we are talking about many years," acknowledges Schuhmacher, who appreciates the support of the FERO Foundation, AECC, ASPANOA, the Carlos III Health Institute (ISCIII) and the DGA to carry out this research.